摘要
目的 基于网络药理学探究清瘟败毒饮治疗手足口病(HFMD)的作用机制,并分析清瘟败毒饮治疗手足口病的临床效果。方法 首先通过网络药理学分析清瘟败毒饮治疗手足口病的分子机制;然后通过临床收治110例手足口病患儿按照随机数字表法分为对照组55例和治疗组55例,观察清瘟败毒饮治疗手足口病的应用效果及验证相关机制。结果 网络药理学研究发现:清瘟败毒饮共有565个靶点,手足口病有1 281个疾病靶点。清瘟败毒饮与手足口病共有98个共同靶点;其中,原癌基因非受体型酪氨酸激酶(SRC)、丝裂原活化蛋白激酶1(MAPK1)、蛋白激酶B(AKT1)、丝裂原活化蛋白激酶3(MAPK3)、肿瘤蛋白53(TP53)、热休克蛋白90α家族A成员1(HSP90AA1)、丝裂原活化蛋白激酶14(MAPK14)、核转录因子κB p65亚基(RELA)、肿瘤坏死因子α(TNF-α)以及白细胞介素-6(IL-6)等关联度较强。98个靶点与154个生物学过程(BP)相关,与20个细胞组成(CC)相关,与17个组织学功能(MF)相关,与121条信号通路相关。经过富集和蛋白质-蛋白质相互作用(PPI)分析发现,清瘟败毒饮治疗HFMD的潜在机制或可能是通过抑制炎症反应,调控炎症因子发挥的。而在PPI蛋白互作和基因富集分析中,TNF-α、白细胞介素-1β(IL-1β)和IL-6度值较高,或可能是清瘟败毒饮治疗HFMD的关键靶点。临床研究发现:治疗结束后,治疗组临床疗效总有效率可达85.5%,高于对照组的67.4%(P<0.05);治疗后,治疗组患儿的发热、疱疹、皮疹、口腔溃疡消退时间均低于对照组(P<0.05);治疗后,2组患儿血清中IL-1β、IL-6、TNF-α均降低(P<0.05),且治疗组优于对照组(P<0.05);治疗后,2组患儿CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)比值均升高(P<0.05),且治疗组优于对照组(P<0.05);对照组的不良反应发生率为18.2%,高于治疗组的7.3%(P<0.05)。结论 本研究利用网络药理学结合临床试验探索分析了清瘟败毒饮治疗HFMD的作用机制,揭示了清瘟败毒饮作用于炎症通路因子IL-1β、IL-6和TNF-α,治疗HFMD的作用机制,为清瘟败毒饮的临床应用及进一步研究其药效作用机制奠定基础。
Objective To explore the mechanism of action of Qingwen Baidu Decoction in the treatment of hand,foot,and mouth disease(HFMD)based on network pharmacology,and to analyze its clinical efficacy in treating HFMD.Methods First,the molecular mechanism of Qingwen Baidu Decoction in treating HFMD was analyzed by network pharmacology.Then,110 children with HFMD admitted clinically were randomly divided into a control group and a treatment group to observe the application effect of Qingwen Baidu Decoction in treating HFMD and verify the relevant mechanisms.Results Network pharmacology studies showed that Qingwen Baidu Decoction had a total of 565 targets,and HFMD had 1281 disease targets.There were 98 common targets between Qingwen Baidu Decoction and HFMD;among them,among them,SRC proto-oncogene,non-receptor tyro-sine kinase(SRC),mitogenactivated protein kinase 1(MAPK1),AKT serine/threonine kinase 1(AKT1),mitogen-activated protein kinase 3(MAPK3),tumor protein p53(TP53),heat shock protein 90 alpha family class A member 1(HSP90AA1),mitogen-activated protein kinase 14(MAPK14),RELA proto-oncogene,NF-κB subunit(RELA),tumor necrosis factor alpha(TNF-α),and interleukin 6(IL-6)had strong correlations.The 98 targets were related to 154 biological processes(BP),20 cellular components(CC),17 molecular functions(MF),and 121 sig-naling pathways.Through enrichment and protein-protein interaction(PPI)analysis,it was found that the potential mechanism of Qingwen Baidu Decoction in treating HFMD might be through inhibiting the inflammatory response and regulating inflammatory factors.In PPI analysis and gene enrichment analysis,TNF,interleukin-1 beta(IL-1β)and IL-6 had high degree values,which might be the key targets of Qingwen Baidu Decoction in treating HFMD.Clinical studies showed that after the end of treatment,the total effective rate of clinical efficacy in the treatment group reached 85.5%,which was significantly higher than 67.4%in the control group(P<0.05).After treatment,the regression time of fever,herpes,rash,and oral ulcers in the treatment group was significantly shorter than that in the control group(P<0.05).After treatment,the serum levels of IL-1β,IL-6 and TNF-αin both groups de-creased significantly(P<0.05),and the treatment group was superior to the control group(P<0.05).After treatment,the CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)ratios in both groups increased significantly(P<0.05),and the treatment group was superior to the control group(P<0.05).The incidence of adverse reactions in the control group was 18.2%,which was significantly higher than 7.3%in the treatment group(P<0.05).Conclusion This study explored and ana-lyzed the mechanism of action of Qingwen Baidu Decoction in treating HFMD by combining network pharmacolo-gy with clinical trials,and revealed that Qingwen Baidu Decoction acts on the inflammatory pathway factors IL-1β,IL-6,and TNF-αto treat HFDM.This study lays a foundation for the clinical application of Qingwen Baidu De-coction and further research on its pharmacodynamic mechanism.
作者
金志培
谢尚任
陈乐乐
戴圣倩
朱剑洁
Jin Zhipei;Xie Shangren;Chen Lele;Dai Shengqian;Zhu Jianjie(Department of Pediatrics,Wenzhou Central Hospital,Wenzhou,Zhejiang 325000,China)
出处
《中国药物与临床》
2025年第23期1514-1521,共8页
Chinese Remedies & Clinics
基金
浙江省温州市级科技计划项目(2023Y1688)。
关键词
清瘟败毒饮
手足口病
网络药理学
治疗结果
Qing Wen Bai Du Yin
Hand,foot and mouth disease
Network pharmacology
Treatment outcome
